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Updated: May 8, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Advances in biomarkers for immunotherapy in small-cell lung cancer
Hui Li1,2, Peiyan Zhao1,2, Lin Tian1,2,3
1Medical Oncology Translational Research Lab, Jilin Cancer Hospital, Changchun, China.
Abstract:
Small-cell lung cancer (SCLC) is a refractory cancer with rapid growth and high aggressiveness. Extensive-stage SCLC is initially sensitive to chemotherapy; however, drug resistance and recurrence occur rapidly, resulting in a poor survival outcome due to lack of subsequently efficient therapy. The emergence of immune checkpoint inhibitors (ICIs) generated a new landscape of SCLC treatment and significantly prolonged the survival of patients. However, the unselected immunotherapy restrains both beneficiary population and responsive period in SCLC compared to the other tumors. The complex tumor origin, high heterogeneity, and immunosuppressive microenvironment may disturb the value of conventional biomarkers in SCLC including programmed cell death 1 ligand 1 and tumor mutation burden. Transcriptional regulator-based subtypes of SCLC are current research hotspot, revealing that Y (I) subtype can benefit from ICIs. Additionally, molecules related to immune microenvironment, immunogenicity, epigenetics, and SCLC itself also indicated the therapeutic benefits of ICIs, becoming potential predictive biomarkers. In this review, we discussed the advances of biomarkers for prediction and prognosis of immunotherapy, promising directions in the future, and provide reference and options for precision immunotherapy and survival improvement in patients with SCLC.
Insights
Identifying new biomarkers is crucial for improving small-cell lung cancer (SCLC) treatment. This review explores predictive biomarkers for immune checkpoint inhibitors (ICIs) to enhance patient survival.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Small-cell lung cancer (SCLC) is aggressive and chemoresistant, leading to poor prognoses.
- Immune checkpoint inhibitors (ICIs) offer new treatment avenues but lack predictive biomarkers for patient selection in SCLC.
- Conventional biomarkers like PD-L1 and TMB are unreliable in SCLC due to tumor complexity.
Purpose of the Study:
- To review advances in biomarkers for predicting immunotherapy response in SCLC.
- To identify promising future directions for precision immunotherapy in SCLC.
- To provide insights for improving patient survival through targeted therapies.
Main Methods:
- Literature review of current research on SCLC biomarkers and immunotherapy.
- Analysis of transcriptional regulator-based subtypes and their association with ICI response.
- Evaluation of immune microenvironment, immunogenicity, and epigenetic factors as potential biomarkers.
Main Results:
- Transcriptional regulator-based subtypes, particularly the Y (I) subtype, show potential for ICI benefit.
- Immune microenvironment, immunogenicity, and epigenetic factors are emerging as predictive biomarkers.
- Novel biomarkers are needed to overcome limitations of current unselected immunotherapy approaches.
Conclusions:
- Developing reliable predictive biomarkers is essential for optimizing ICI therapy in SCLC.
- Precision immunotherapy strategies targeting specific SCLC subtypes and molecular profiles can improve outcomes.
- Further research into novel biomarkers will guide treatment decisions and enhance survival for SCLC patients.
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